大鼠鞘内联合给予GABA(A)激动剂和谷氨酸拮抗剂后最低肺泡浓度的降低

MAC reduction after intrathecal coadministration of GABA(A) agonist and glutamate antagonist in rats.

作者信息

Sumikura Hiroyuki, Arendt-Nielsen Lars

机构信息

Department of Anesthesiology, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki 216-0015, Japan.

出版信息

J Anesth. 2003;17(2):92-7. doi: 10.1007/s005400300023.

DOI:10.1007/s005400300023

PMID:12903919

Abstract

PURPOSE

It has been reported that intrathecal coadministration of a GABA(A) agonist and a glutamate antagonist induces synergistic antinociceptive effects in rats. We hypothesized that this synergistic antinociceptive effect might induce a synergistic reduction in the minimum alveolar anesthetic concentration (MAC).

METHODS

The MAC for sevoflurane was determined before and after intrathecal administration of muscimol (GABA(A) agonist, 0.1-10 microg), AP-5 (N-methyl-D-aspartate [NMDA] antagonist, 0.1-10 microg), and YM872 (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid [AMPA] antagonist, 0.1-10 microg) in rats. The effects of coadministration of muscimol and AP-5 or YM872 on MAC reduction were also tested.

RESULTS

Intrathecal administration of muscimol at doses of 1 and 10 microg significantly reduced the MAC by 34.5% +/- 3.3% and 46.9% +/- 4.4%, respectively (P < 0.01). Intrathecal administration of AP-5 at a dose of 10 microg and YM872 at a dose of 10 microg significantly reduced the MAC by 25.8% +/- 2.4% and 31.4% +/- 6.3%, respectively (P < 0.01). No additional reductions in MAC values were observed when a GABA(A) agonist was combined with either an NMDA or an AMPA antagonist.

CONCLUSION

Intrathecal coadministration of a GABA(A) agonist and an NMDA or AMPA antagonist, which has been reported to produce a synergistic antinociceptive effect, did not induce a synergistic reduction in the MAC. The antinociceptive effect may not be the predominant factor in the reduction of the MAC induced by these drugs.

摘要

目的

据报道，鞘内联合给予γ-氨基丁酸A（GABA(A)）激动剂和谷氨酸拮抗剂可在大鼠中诱导协同镇痛作用。我们推测这种协同镇痛作用可能会导致最低肺泡有效浓度（MAC）协同降低。

方法

在大鼠鞘内注射蝇蕈醇（GABA(A)激动剂，0.1 - 10微克）、AP - 5（N - 甲基 - D - 天冬氨酸[NMDA]拮抗剂，0.1 - 10微克）和YM872（α - 氨基 - 3 - 羟基 - 5 - 甲基 - 4 - 异恶唑丙酸[AMPA]拮抗剂，0.1 - 10微克）前后，测定七氟醚的MAC。还测试了蝇蕈醇与AP - 5或YM872联合给药对MAC降低的影响。

结果

鞘内注射1微克和10微克剂量的蝇蕈醇分别使MAC显著降低34.5%±3.3%和46.9%±4.4%（P < 0.01）。鞘内注射10微克剂量的AP - 5和10微克剂量的YM872分别使MAC显著降低25.8%±2.4%和31.4%±6.3%（P < 0.01）。当GABA(A)激动剂与NMDA或AMPA拮抗剂联合使用时，未观察到MAC值的进一步降低。